Final Diagnosis -- Intravascular large B-cell lymphoma with extensive sellar involvement

DIAGNOSIS:   INTRAVASCULAR LARGE B-CELL LYMPHOMA WITH EXTENSIVE SELLAR INVOLVEMENT.

DISCUSSION:

In the reported case of a 63 year-old man showing a fulminant clinical course consisting of progressive dementia, cerebellar ataxia, myoclonus, alternating hemiparesis, right VI nerve palsy and somnolence, differential diagnosis comprised primarily a metastatic disease (e.g. primary tumor like renal cell cancer or melanoma), a systemic lymphatic disease and a brain stem encephalitis. A sellar mass of 3.2 cm in maximum diameter was diagnosed one month before death. Autopsy revealed an intravascular large cell lymphoma (IVLL).

Intravascular large cell lymphoma (IVLL) is a rare neoplasm characterized by the proliferation of lymphoma cells predominantly within the blood vessels. It most likely originates from a unique subtype of B cells, their normal counterpart being of germinal center/post germinal center B-cell (6)

According to the WHO classification it is considered a subtype of diffuse large B-cell lymphoma (3). Probably, some cases previously diagnosed as primary CNS lymphomas may have included IVLL cases (4). PCR studies revealed that IVLL might be associated with EBV infection, but in the majority of cases such association could not be established (1). Clinical manifestations are typically neurologic and dermatologic, but it is often diagnosed solely at autopsy (5). In general, IVLL is a very aggressive lymphoma which responds poorly to chemotherapy and death occurs in most cases within a short time following presentation, according to the immunohistochemical gene expression profiles delineating IVLL as diffuse large B-cell lymphoma of activated type. Although an more or less extend extravascular tumor component is a known feature of IVLL, the peculiar phenotype of intravascular proliferation is not clarified and still controversial. Probably the tumor cells are unable to extravasate because of the disturbance of adhesion profile on the tumor cells and/or endothelial cells. Of these the ß1-integrin CD29 is documented to be lacking on IVLL (7).

In our case, the patient presented with a mass lesion which initially could be seen only 2 months before death, but reaching a diameter of 4 cm by the time of his death. The determinant histologic feature of IVLL is the intraluminal presence of tumor cells and thus the extensive extravascular involvement of CNS with diffuse infiltration of lymphoma cells seen in our cases is remarkable since this finding is described in only 13 cases in the literature (4). Beside the mass in the CNS, the large tumor in the adrenal glands and surrounding tissue is a known feature of IVLL (2, 8) and probably contributed to the fever (8) that is often encountered in IVLL (9). This is the first published case of an intravascular B-cell lymphoma to become predominantly manifest as a large sellar tumor mass.

Acknowledgments:

We thank Gudrun Albrecht, Institute of Brain Research, University Tuebingen, Germany, for excellent photographical preparations.

REFERENCES:

1. Abe S, Kumanishi T (1995) Molecular genetic analysis of intravascular malignant lymphomatosis cells. Rinsho Shinkeigaku 35(12):1473-5.
2. Demirer T, Dail DH, Aboulafia DM (1994) Four varied cases of intravascular lymphomatosis and a literature review. Cancer 73:1738-1745.
3. Gatter KC, Warnke RA (2001) In: Pathology and Genetics. Tumours of Haematopoietic and Lymphoid Tissues. WHO. Editors: Jaffe ES, Harris NL, Stein H, Vardiman JW. 177-78.
4. Imai H, Kajimoto K, Taniwaki M, Miura I, Hatta Y, Hashizume Y, Watanabe M, Shiraishi T, Nakamura S (2004) Intravascular large B-cell lymphoma presenting with mass lesions in the central nervous system: a report of five cases. Pathol Int 54(4):231-6.
5. Khoury H, Lestou VS, Gascoyne RD, Bruyere H, Li CH, Nantel SH, Dalal BI, Naiman SC, Horsman DE (2003) Multicolor karyotyping and clinicopathological analysis of three intravascular lymphoma cases. Mod Pathol 16(7):716-24.
6. Köber SM, Aepinus C, Bščltmann B, Kaiserling E (2001) Intravascular large B-cell lymphoma. Histogenesis - a molecular biological study. Path Res Pract 197 (5): 342A.
7. Ponzoni M, Arrigoni G, Gould VE, Del CB, Maggioni M, Scapinello A, Paolino S, Cassisa A, Patriarca C (2000) Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Hum Pathol 31:220-226.
8. Wick MR, Mills SE, Scheithauer BW, Cooper PH, Davitz MA, Parkinson K (1986) Reassessment of malignant "angioendotheliomatosis". Evidence in favor of its reclassification as "intravascular lymphomatosis". Am J Surg Pathol 10:112-123.
9. Zeidman, A., Horowitz, A., Fradin, Z., Cohen, A., Wolfson, L., and Elimelech, O (2004) Fulminant intravascular lymphoma presenting as fever of unknown origin. Leuk.Lymphoma 45(8) 1691-1693.

Contributed by Michel Mittelbronn, Annika Wersebe, Michael Weller, Walter Hewer, Richard Meyermann, Edwin Kaiserling, Rudi Beschorner, Stefan M. Kröber